Biomedical subjects

C P Cheng

Publications and source records attributed to C P Cheng.

At least 19 recordsLinked to original sources

PubMed2001

Upregulation of functional beta(3)-adrenergic receptor in the failing canine myocardium.

Altered expression and functional responses to cardiac beta(3)-adrenergic receptors (ARs) may contribute to progressive cardiac dysfunction in heart failure (CHF). We compared myocyte beta(3)-AR mRNA and protein levels and myocyte contractile, [Ca(2+)](i) transient, and Ca(2+) current (I(Ca,L)) responses to BRL-37344 (BRL, 10(-8) mol/L), a selective beta(3)-AR agonist, in 9 instrumented dogs before and after pacing-induced CHF. Myocytes were isolated from left ventricular myocardium biopsy tissues. Using reverse transcription-polymerase chain reaction, we detected beta(3)-AR mRNA from myocyte total RNA in each animal. Using a cloned canine beta(3)-AR cDNA probe and myocyte poly A(+) RNA, we detected a single band about 3.4 kb in normal and CHF myocytes. beta(3)-AR protein was detected by Western blot. beta(3)-AR mRNA and protein levels were significantly greater in CHF myocytes than in normal myocytes. Importantly, these changes were associated with enhanced beta(3)-AR-mediated negative modulation on myocyte contractile response and [Ca(2+)](i) regulation. Compared with normal myocytes, CHF myocytes had much greater decreases in the velocity of shortening and relengthening with BRL accompanied by larger reductions in the peak systolic [Ca(2+)](i) transient and I(Ca,L). These responses were not modified by pretreating myocytes with metoprolol (a beta(1)-AR antagonist) or nadolol (a beta(1)- and beta(2)-AR antagonist), but were nearly prevented by bupranolol or L-748,337 (beta(3)-AR antagonists). We conclude that in dogs with pacing-induced CHF, beta(3)-AR gene expression and protein levels are upregulated, and the functional response to beta(3)-AR stimulation is increased. This may contribute to progression of cardiac dysfunction in CHF.

Adrenergic beta-1 Receptor Antagonists↗

PubMed2001

Allopurinol enhances the contractile response to dobutamine and exercise in dogs with pacing-induced heart failure.

BACKGROUND: Superoxide (O(2)(-)) generated by enhanced xanthine oxidase (XO) activity may contribute to the increased myocardial oxidative stress in heart failure (CHF). Because blocking XO with allopurinol augments myofilament Ca(2+) sensitivity in reperfusion injury and CHF, we hypothesized that it may improve adrenergic inotropic responsiveness in CHF. METHODS AND RESULTS: We studied the effect of allopurinol on the contractile response to dobutamine and exercise in 7 chronically instrumented conscious dogs before and after producing CHF by rapid pacing. Left ventricular (LV) contractile performance was measured by the slopes of the LV end-systolic pressure-volume relation (E(ES)) and stroke work-end-diastolic volume relation (M(SW)). Before CHF, allopurinol produced no change in LV contractile performance and did not alter the response to dobutamine or exercise. After CHF, allopurinol produced significant (P:<0.05) increases in E(ES) (5.0+/-0.6 versus 3.3+/-0.6 mm Hg/mL) and M(SW). Dobutamine and allopurinol produced greater increases in E(ES) (5.4+/-0.6 versus 7.4+/-0.6 mm Hg/mL) and M(SW) (60.1+/-7.4 versus 73.7+/-4.4 mm Hg) than did dobutamine alone. After allopurinol, dP/dt(max), stroke volume, and M(SW) were higher during CHF exercise. LV diastolic pressures were lower during CHF exercise after allopurinol. CONCLUSIONS: Allopurinol has no discernable effects on LV contractile function or adrenergic responsiveness in normal, conscious animals. In pacing-induced CHF, however, allopurinol improves LV systolic function at rest and during adrenergic stimulation and exercise.

Allopurinol↗

PubMed2001

Analysis of glutathione by capillary electrophoresis based on sample stacking.

Glutathione is a small peptide, which participates in cellular oxidation-reduction and detoxification. It is present in most biological tissues at different concentrations. The oxidized and reduced forms of the peptide were measured in erythrocytes and myocardial tissue by capillary electrophoresis based on stacking. After tissue homogenization or hemolysis of the red blood cells, the samples were deproteinized with acetonitrile and injected filling about 13% of the capillary volume. The electrophoresis was performed at 10 kV using a separation buffer of 250 mM borate, 50 mM Tris, pH 8.0. Sample stacking increased the sensitivity of detection by 10-20-fold.

Animals↗

PubMed2001

The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure.

The diastolic dysfunction present at rest in congestive heart failure (CHF) is exacerbated during exercise (Ex). Increases in circulating ANG II and endothelin-1 (ET-1) during Ex may contribute to this response. We assessed the effect of Ex on circulating plasma levels of ANG II and ET-1 and left ventricular (LV) dynamics before and after pacing-induced CHF at rest and during Ex in nine conscious, instrumented dogs. Before CHF, there were modest increases in circulating levels of ANG II (but not ET-1) during Ex. LV diastolic performance was enhanced during Ex with decreases in the time constant of LV relaxation (tau), LV end-systolic volume (V(ES)), and LV minimum pressure with a downward shift of the LV early diastolic portion of the pressure-volume (P-V) loop. This produced an increase in peak LV filling rate without an increase in mean left atrial (LA) pressure. After CHF, the resting values of ANG II and ET-1 were elevated and increased to very high levels during Ex. After CHF, mean LA pressure, tau, and LV minimum pressure were elevated at rest and increased further during Ex. Treatment with L-754,142, a potent ET-1 antagonist, or losartan, an ANG II AT(1)-receptor blocker, decreased these abnormal Ex responses in CHF more effectively than an equally vasodilatory dose of sodium nitroprusside. Combined treatment with both ANG II- and ET-1-receptor blockers was more effective than either agent alone. We conclude that in CHF, circulating ANG II and ET-1 increase to very high levels during Ex and exacerbate the diastolic dysfunction present at rest.

Acetamides↗

PubMed2001

Enhanced cardiac L-type calcium current response to beta2-adrenergic stimulation in heart failure.

The beta2-adrenergic receptor (beta2-AR)-mediated increase in cardiac L-type Ca2+ current (I(Ca,L)) has been documented in normal subjects. However, the role and mechanism of beta2-AR activation on I(Ca,L) in heart failure (HF) are unclear. Accordingly, we compared the effect of zinterol (ZIN), a highly selective beta2-AR agonist, on I(Ca,L) in isolated left ventricular cardiomyocytes obtained from normal control and age-matched rats with HF induced by left coronary artery ligation (4 months). I(Ca,L) was measured by using the whole-cell voltage-clamp technique. In normal myocytes, superfusion of ZIN (10(-5) M) caused a 21% increase in I(Ca,L) (9.21 +/- 0.24 versus 7.59 +/- 0.20 pA/pF) (p < 0.05). In HF myocytes, the same concentration of ZIN produced a significantly greater increase (30%) in I(Ca,L) (6.20 +/- 0.24 versus 4.75 +/- 0.17 pA/pF) (p < 0.01). This ZIN-induced increase in I(Ca,L) was further augmented in both normal and HF myocytes (normal: 59 versus 21%; HF: 71 versus 30%) after the incubation of myocytes with pertussis toxin (PTX, 2 microg/ml, 36 degrees C, 6 h). These effects were not modified by the incubation of myocytes with CGP-20712A (3 x 10(-7) M), a beta1-AR antagonist, but were abolished by pretreatment of myocytes with ICI-118551 (10(-7) M), a beta2-AR antagonist. In addition, all of the effects induced by ZIN were completely prevented in the presence of an inhibitory cAMP analog, Rp-cAMPS (100 microM, in the patch-pipette solution). In conclusion, beta2-AR activation stimulates L-type Ca2+ channels and increases I(Ca,L) in both normal and HF myocytes. In HF, beta2-AR activation-induced augmentation of I(Ca,L) was increased. These effects are likely to be mediated through a cAMP-dependent mechanism and coupled with both stimulatory G protein and PTX-sensitive G protein.

Adrenergic beta-Agonists↗

PubMed2000

Diastolic dysfunction as a cause of exercise intolerance.

Tachycardia accompanying exercise shortens the duration of diastole, reducing the time available for the left ventricular (LV) filling. Thus, the LV must fill more rapidly for the stroke volume to increase (or even be maintained) during exercise. Normally, this is accomplished without requiring an excessive increase in left atrial (LA) pressure by an acceleration of LV relaxation and a fall in LV early diastolic pressure during exercise. This response is lost following the development of heart failure due to systolic dysfunction, both in experimental animals and in patients. In fact, in such situations, LV relaxation slows and LV early diastolic pressure increases due to exercise. Thus, any diastolic dysfunction present at rest in CHF during systolic dysfunction is exacerbated during exercise. Similarly, patients with primary diastolic dysfunction heart failure with preserved systolic function may not be able to augment LV filling rates without an abnormal increase in LA pressure. Thus, diastolic dysfunction may contribute to exercise intolerance, both in systolic dysfunction and primary diastolic dysfunction. Acute studies suggest that treatment with angiotensin II receptor blockers or verapamil may improve exercise tolerance in some patients with primary diastolic dysfunction.

Animals↗

PubMed1999

Structural and functional analysis of the 3' untranslated region of bamboo mosaic potexvirus genomic RNA.

The secondary structure of a 170 nt transcript derived from a cDNA clone containing the 3' untranslated region of bamboo mosaic potexvirus (BaMV) with 32 adenine residues of the poly(A) tail, was investigated in solution by using enzymatic and chemical probes. Three consecutive stem-loops forming a cloverleaf-like structure (domain ABC) and a major stem-loop (domain D) containing a bulge and an internal loop were identified as connected to a previously identified pseudoknot domain (domain E) comprising at least 13 adenylate residues of the 3' poly(A) tail. The highly conserved hexamer nucleotides (ACc/uUAA) among potexviruses are located in loop D and the putative polyadenylation signal (AAUAAA) is located in the internal loop of domain D. Based on the data of the structural probing, a three-dimensional structure was modeled. Mutants with domain ABC deleted showed no detectable signal in protoplasts, while changes in domain D, except for the bulge deletion, showed interference of BaMV RNA accumulation in protoplasts. Mutants with disrupted stem D formation impaired BaMV accumulation. However, the mutant with compensatory mutations restored stem formation which could only improve the viral accumulation to 58 % that of the wild-type structure.

3' Untranslated Regions↗

PubMed1999

Sufficient length of a poly(A) tail for the formation of a potential pseudoknot is required for efficient replication of bamboo mosaic potexvirus RNA.

RNAs transcribed from a full-length infectious cDNA clone of the bamboo mosaic potexvirus (strain O) genome, pBaMV-O, were infectious to Nicotiana benthamiana plants. Mutant genomes in which the poly(A) tail is absent or replaced by a 3' tRNA-like structure from turnip yellow mosaic virus RNA failed to amplify detectably in N. benthamiana protoplasts. No amplification was detected in protoplasts inoculated with transcripts containing 4, 7, or 10 adenylate residues at the 3' end, whereas transcript inocula with 15 adenylate residues resulted in coat protein accumulation to a level 26% of that resulting from inoculation with transcripts with 25 adenylate residues (designated as wild type). Coat protein accumulation levels of 69 and 98% relative to wild type were observed after inoculation of protoplasts with transcripts bearing poly(A) tails 18 and 22 nucleotides long, respectively. The presence of a putative 3' pseudoknot structure including at least 13 adenylate residues of the 3'-terminal poly(A) tail was supported by enzymatic and chemical structural analysis. The functional relevance of this putative pseudoknot was tested by mutations that affected basepairing within the pseudoknot. These results support the existence of functional 3' pseudoknot that includes part of the 3' poly(A) tail.

Base Sequence↗

PubMed1999

Endogenous endothelin-1 depresses left ventricular systolic and diastolic performance in congestive heart failure.

Endothelin-1 (ET-1) is a positive inotrope in normal hearts; however, the direct cardiac effects of endogenous ET-1 in congestive heart failure (CHF) are unknown. We evaluated the cardiac responses to endogenous ET-1 using an ETA and ETB receptor blocker (L-754,142) in seven conscious dogs before and after pacing-induced CHF. Before CHF, when the plasma ET-1 was 7.3 +/- 1.7 fmol/ml, L-754,142 caused no significant alterations in heart rate, left ventricular (LV) end-systolic pressure, total systemic resistance, and the time constant of LV relaxation (tau). LV contractile performance, measured by the slopes of LV pressure (P)-volume (V) relation (EES), dP/dtmax-end-diastolic V relation (dE/dtmax), and stroke work-end-diastolic V relation, was also unaffected. After CHF, when the plasma ET-1 was significantly increased to 14.1 +/- 3.0 fmol/ml (p <.05), L-754,142 produced a significant decreases in LV end-systolic pressure (101 +/- 11 versus 93 +/- 8 mm Hg) and total systemic resistance (0.084 +/- 0.022 versus 0.065 +/- 0.15 mm Hg/ml/min). The tau (42 +/- 12 versus 38 +/- 10 ms), mean left atrial P (22 +/- 5 versus 18 +/- 4 mm Hg) (p <.05), and minimum LVP were also significantly decreased. After CHF, the slopes of P-V relations, EES (3.4 +/- 0.4 versus 4.8 +/- 0.8 mm Hg/ml), dE/dtmax (42.4 +/- 7.8 versus 50.0 +/- 7.8 mm Hg/s/ml), and stroke work-end-diastolic V relation (58.1 +/- 3.3 versus 72.4 +/- 5.2 mm Hg) (p <.05) all increased after L-754,142, indicating enhanced contractility. Before CHF, low levels of endogenous ET-1 have little cardiac effect. However, after CHF, elevated endogenous ET-1 produces arterial vasoconstriction, slows LV relaxation, and depresses LV contractile performance. Thus, elevated endogenous ET-1 may contribute to the functional impairment in CHF in this canine model.

Animals↗

PubMed1999

Effects of atrial natriuretic peptide on left ventricular performance in conscious dogs before and after pacing-induced heart failure.

Atrial natriuretic peptide (ANP) has potent vasodilatory and natriuretic actions and may have therapeutic benefit in congestive heart failure (CHF). These benefits may be offset by a negative inotropic effect of ANP seen in isolated preparations. However, ANP's integrated effect on left ventricular (LV) contraction and relaxation, independent of loading conditions, both under normal conditions and after CHF, is not known. We studied six conscious dogs, instrumented to measure LV and left atrial pressures and to determine LV volume from three dimensions. ANP produced significant (P<.05) decreases in LV end-systolic pressure (101.2+/-11.8 versus 91.7+/-11.2 mm Hg, P<.05) in normal dogs and in dogs with CHF (93.1+/-6.4 versus 87.1+/- 4.4 mm Hg, P<.05). ANP also caused significant reductions of the slope of end-systolic pressure-end-systolic volume relation both before (7.0 +/-1.5 versus 6.3+/-1.5 mm Hg/ml) and after CHF (4.8+/-1.3 versus 4.4+/-1.2 mm Hg/ml, P<.05). Both before and after CHF, ANP slowed LV relaxation at matched end-systolic pressure. Before CHF, steady-state stroke volume and peak LV filling rate (dV/dt(max)) were reduced. However, after CHF, the fall in end-systolic pressure more than offset the load-independent LV depression, as stroke volume, the rate LV relaxation, and dV/dt(max) were increased and minimum LV pressure reduced. ANP has negative effects on LV contractility and relaxation both before and after CHF. However, after CHF, afterload reduction with ANP overcomes its negative effects, resulting in net improvement of LV ejection and relaxation. Thus, the direct cardiodepressant effects of ANP should not limit its usefulness in CHF.

Animals↗

PubMed1999

[Effect of human inhibin alpha-fragment 1-32-Tyr(P33) on apoptosis of cultured rat corpus luteal cells].

Recently, increasing evidence suggests that alpha inhibin or related proteins may be a functional regulator in the ovary, which is independent of hetero-dimer inhibin. In our previous study, it was demonstrated that human inhibin alpha-N-terminal fragment Tyr-1-32 (P(33)) significantly inhibited progesterone production by rat corpus luteal cells in vitro, and stimulated luteal functional regression and apoptosis in vivo. In the present work, the action of P(33) on apoptosis was further studied in vitro in cultured rat CL cells. Gel electrophoretic analysis for detection of oligonucleosomal DNA fragmentation, AO-EB or PI assays and flow cytometry were used to observe the action of P(33) on the occurrence of spontaneous apoptosis by collagenase-DNase dispersed CL cells, obtained from PMSG-hCG induced pseudopregnant rats. The results showed that P(33) (1 microg/ml) stimulated spontaneous apoptosis of CL cells. The inhibitor of tyrosine protein kinase, genistein (50 microg/ml),inhibited P(33) enhanced spontaneous apoptosis. RNA and protein synthesis inhibitors cycloheximide (Cyx,50 microg/ml) and actinomycin D(Act D,50 microg/ml) did not protect the cells from apoptosis stimulated by P(33). The results suggest that P(33) stimulates spontaneous apoptosis in cultured rat CL cells with the involvement of tyrosine specific protein kinase system. This work provides further evidence for the hypothesis that alpha inhibin or related protein might be a functional regulator in the ovary.

Animals↗

PubMed1998

Evaluation of Mn2+ stimulated and Zn2+ inhibited apoptosis in rat corpus luteal cells by flow cytometry and fluorochromes staining.

We had reported that Mn2+ is the most effective divalent ion in stimulating apoptosis and Zn2+ inhibits apoptosis in corpus luteal (CL) cells of rat, which evidenced by the appearance of internucleosoma DNA fragmentation in electrophoretic gel. To further understand morphological character of apoptosis undergone in CL cells, we performed fluorochromes staining and flow cytometric studies on Mn2+ and Zn2+ treated CL cells. Cells dispersed by collegenase-DNase from PMSG-hCG primed pseudopregnant rats were incubated in KRBGAL solution for 4 h with 5 mM Mn2+ or Zn2+. Staining of nuclei with the DNA binding fluorescent dyes, acridine orange-ethidium bromide (AO-EB), showed an increased green fluorescence of AO in Mn2+ treated cells as compared with control or Zn2+ group. DNA content analysis showed that Mn2+ caused an absolute shift from right to left side in the scatter profile by Flow Cytometry. The consistency of above results supported that Mn2+ is the most effective divalent ions in stimulating apoptosis in CL cells of rat, and provided a morphological character of apoptosis undergo in CL cells. The results also suggest that fluorochromes staining and flow cytometry are effective and convenient methods in study of apoptosis in CL cells.

Animals↗

PubMed1998

Evaluation of left ventricular diastolic function from the pattern of left ventricular filling.

The pattern of left ventricular (LV) filling can be determined by Doppler echocardiography. Normally most LV filling occurs early in diastole, with some additional filling occurring during atrial systole, late in diastole. In the absence of mitral stenosis, three patterns of LV filling indicate progressively greater diastolic dysfunction: (1) Reduced early diastolic filling with a compensatory increase in importance of atrial filling, termed a pattern of "impaired relaxation;" (2) "pseudo-normalization" with most filling early in diastole but with rapid deceleration of mitral flow; and (3) "restricted filling" with almost all filling of the LV occurring very early in diastole in association with very rapid deceleration of mitral flow. A large, prolonged atrial regurgitant flow in the pulmonary veins also indicates impaired diastolic performance. The time for early filling deceleration is predominantly determined by LV stiffness: the shorter the deceleration time, the stiffer the LV. Patients with short deceleration time have a poor prognosis.

Blood Flow Velocity↗

PubMed1998

High rates of antimicrobial resistance among clinical isolates of nontyphoidal Salmonella in Taiwan.

To assess trends in antimicrobial-resistant Salmonella infections from 1989 to 1996 in southern Taiwan, the minimum inhibitory concentrations (MICs) of 14 antibiotics or antibiotic combinations were determined by the agar dilution method for 297 clinical isolates of nontyphoidal Salmonella. The rates of resistance to ampicillin, chloramphenicol, and tetracycline were 65, 67, and 78%, respectively. Resistance to trimethoprim-sulfamethoxazole (TMP-SMX) increased from 25% in 1989-1992 to 35% in 1993-1996 (P=0.057). For new quinolones and extended-spectrum cephalosporins, no resistant strains were encountered. Multiple resistance to more than five antimicrobial drugs doubled from 10.6% in 1989-1992 to 19.7% in 1993-1996. Multiply resistant salmonellae were isolated more commonly from blood samples than from feces (30% vs. 14%, P<0.05). In Taiwan, ampicillin, chloramphenicol, and even TMP-SMX are no longer the drugs of choice for treatment of serious nontyphoidal Salmonella infections. Extended-spectrum cephalosporins are now the preferred drugs in Taiwan for treatment of invasive Salmonella infections in children.

Anti-Bacterial Agents↗

PubMed1998

Altered inotropic response of endothelin-1 in cardiomyocytes from rats with isoproterenol-induced cardiomyopathy.

OBJECTIVE: The positive inotropic effect of endothelin-1 (ET-1) on normal myocardial contraction may be altered in pathological states. The purpose of this study was to assess the direct effect of ET-1 on cardiomyocyte performance and its cellular mechanism in congestive heart failure (CHF). METHODS: We measured the plasma levels of ET-1 and compared the effects of ET-1 (10(-10)-10(-8) M) on contractile performance and the [Ca2+]i transient in the myocytes of left ventricles (LV) from 15 age-matched normal adult rats and 15 rats with isoproterenol (ISO)-induced CHF. RESULTS: With CHF, the plasma levels of ET-1 (19.7 +/- 6.3 vs. 4.1 +/- 0.5 fmol/ml, p < 0.05) were markedly elevated. In normal myocytes, superfusion of ET-1 caused significant increases in the systolic amplitude (SA, 8-16%) and the peak velocity of shortening (dL/dtmax, 20-35%; p < 0.01) without causing a change in the peak [Ca2+]i transient. In contrast, in myocytes from CHF rats, ET-1 produced significant reductions in SA (9-13%) and in the velocity of relengthening, dR/dtmax (10-14%; p < 0.05). The myocytes' dR/dtmax also decreased by 8-10% (p < 0.05). These changes were associated with a significant decrease in the peak [Ca2+]i transient (20-23%, p < 0.01). These responses to ET-1 were abolished by the incubation of myocytes with an ETA receptor antagonist (BQ123) or a protein kinase C (PKC) inhibitor (H-7 or staurosporine). CONCLUSION: ISO-induced CHF is associated with elevated plasma ET-1 and an altered cardiomyocyte response to ET-1. After CHF, ET-1 produces a direct depression of cardiomyocyte contractile performance that is associated with a significant decrease in the peak [Ca2+]i transient. These effects are likely to be mediated through ETA receptors and involve the PKC pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1998

Tubules containing virions are present in plant tissues infected with Commelina yellow mottle badnavirus.

Tubular structures containing bacilliform virions were observed in cell-free extracts of Commelina diffusa infected with Commelina yellow mottle badnavirus (CoYMV). The exterior of the tubule reacted with antibodies to CoYMV movement protein, but not with antibodies to virus coat protein. Similar tubular structures containing bacilliform particles were also observed in ultrathin sections of CoYMV-infected C. diffusa. These tubular structures traversed the cell wall at points where this was thickened or protruded. No similar structures were observed in healthy C. diffusa. These observations support the hypothesis that the virion-containing tubular structures observed in cell-free extracts are the same as those observed in situ, that these structures are composed, at least in part, of virus movement protein, and that they play a role in the cell-to-cell trafficking of virions of CoYMV.

Antibodies, Viral↗

PubMed1998

Functional effects of endogenous bradykinin in congestive heart failure.

OBJECTIVES: The purpose of this study was to determine the level and functional effects of endogenous bradykinin in congestive heart failure (CHF). BACKGROUND: There is experimental evidence that bradykinin is increased in several cardiac disease states. However, it is unknown whether plasma levels of bradykinin are elevated in CHF. Further, the cardiac and vascular responses to bradykinin in CHF are unclear. METHODS: The circulating levels of bradykinin and the effects of endogenous bradykinin were assessed in eight instrumented, conscious dogs both before and after pacing-induced CHF. RESULTS: Before CHF, the plasma bradykinin level was 53.1 +/- 12.4 pg/ml. Blocking endogenous bradykinin with HOE-140 (0.3 mg/kg), a specific bradykinin B2-receptor antagonist, produced no significant alterations in heart rate, left ventricular (LV) end-systolic pressure (Pes), total systemic resistance (TSR), the time constant of LV relaxation (tau) or the maximal rate of LV filling (dV/dt(max)). However, coronary blood flow was significantly reduced (p < 0.05). LV contractile performance measured by the slopes of pressure-volume relations was unaffected. After induction of CHF, the plasma bradykinin level increased to 234.2 +/- 19.4 pg/ml (p < 0.05). Blocking endogenous bradykinin with HOE-140 reduced coronary blood flow and produced significant increases in Pes and TSR, prolonged tau, decreased dV/dt(max) and elevated minimal LV pressure and mean left atrial pressure. Furthermore, the slopes of pressure-volume relations (p < 0.05) were decreased, indicating depressed contractility with HOE-140 after CHF. CONCLUSIONS: Before CHF, endogenous bradykinin results in coronary dilation but has no effect on systemic arterial vasodilation or cardiac performance. After CHF, endogenous bradykinin is significantly increased and, acting through B2-receptors, produces coronary and arterial vasodilation and improves LV relaxation and contractile performance. Thus, endogenous bradykinin may play an important role in preserving cardiovascular function in CHF.

Animals↗

PubMed1997

Wave-intensity analysis: a new approach to left ventricular filling dynamics.

In order to explore a new approach to the analysis of diastolic dysfunction, we adapted wave-intensity analysis (WIA), a time-domain analysis that provides information regarding both upstream and downstream events, to left ventricular (LV) filling. WIA considers the pressure and flow waves as summations of successive wavelets, characterised by the direction they travel and by the sign of the pressure gradient associated with them. Wave intensity is the product, dPdU, calculated from the incremental differences in LV pressure (dP) and mitral velocity (dU) and, during the diastolic filling interval, yields up to five dPdU peaks. Peak 1 is caused by backward-travelling expansion waves that accelerate the blood while LV pressure falls, and may be related to "diastolic suction". Peak 2 is caused by forward-travelling compression waves which occur if acceleration continues after LV pressure begins to increase. Peak 3 is caused by backward compression waves and is associated with rising LV pressure and deceleration. Peak 4 is caused by forward compression waves and is associated with the increasing LV pressure and acceleration caused by atrial contraction. Peak 5 is caused by backward compression waves and is associated with increasing pressure and deceleration. These preliminary observations suggest that WIA can be useful in describing the mechanics of LV filling and, after much further work has been accomplished, it might prove useful in the detection and characterization of diastolic dysfunction.

Aorta↗